Daniel Alcolea1, Eduard Vilaplana1, Marc Suárez-Calvet1, Ignacio Illán-Gala1, Rafael Blesa1, Jordi Clarimón1, Albert Lladó1, Raquel Sánchez-Valle1, José L Molinuevo1, Guillermo García-Ribas1, Yaroslau Compta1, María José Martí1, Gerard Piñol-Ripoll1, Guillermo Amer-Ferrer1, Aina Noguera1, Ana García-Martín1, Juan Fortea1, Alberto Lleó2. 1. From the Department of Neurology (D.A., E.V., M.S.-C., I.I.-G., R.B., J.C., J.F., A. Lleó), Institut d'Investigacions Biomèdiques Sant Pau-Hospital de Sant Pau, Universitat Autònoma de Barcelona; Alzheimer's Disease and Other Cognitive Disorders Unit (A. Lladó, R.S.-V., J.L.M.), Department of Neurology, Hospital Clínic, Institut d'Investigació Biomèdica August Pi I Sunyer, Barcelona; Servicio de Neurología (G.G.-R.), Hospital Universitario Ramón y Cajal, Madrid; Parkinson's Disease and Movement Disorders Unit (Y.C., M.J.M.), Neurology Service, Institute of Clinical Neurosciences, Hospital Clínic/IDIBAPS and University of Barcelona; Unitat de Trastorns Cognitius (G.P.-R.), Hospital Santa Maria, Lleida; Unidad de Neurología Cognitiva (G.A.-F., A.N., A.G.-M.), Servicio de Neurología, Hospital Universitari Son Espases, Palma de Mallorca; and Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (D.A., E.V., M.S.-C., I.I.-G., R.B., J.C., Y.C., M.J.M., J.F., A. Lleó), Madrid, Spain. 2. From the Department of Neurology (D.A., E.V., M.S.-C., I.I.-G., R.B., J.C., J.F., A. Lleó), Institut d'Investigacions Biomèdiques Sant Pau-Hospital de Sant Pau, Universitat Autònoma de Barcelona; Alzheimer's Disease and Other Cognitive Disorders Unit (A. Lladó, R.S.-V., J.L.M.), Department of Neurology, Hospital Clínic, Institut d'Investigació Biomèdica August Pi I Sunyer, Barcelona; Servicio de Neurología (G.G.-R.), Hospital Universitario Ramón y Cajal, Madrid; Parkinson's Disease and Movement Disorders Unit (Y.C., M.J.M.), Neurology Service, Institute of Clinical Neurosciences, Hospital Clínic/IDIBAPS and University of Barcelona; Unitat de Trastorns Cognitius (G.P.-R.), Hospital Santa Maria, Lleida; Unidad de Neurología Cognitiva (G.A.-F., A.N., A.G.-M.), Servicio de Neurología, Hospital Universitari Son Espases, Palma de Mallorca; and Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (D.A., E.V., M.S.-C., I.I.-G., R.B., J.C., Y.C., M.J.M., J.F., A. Lleó), Madrid, Spain. alleo@santpau.es.
Abstract
OBJECTIVE: To analyze the clinical utility of 3 CSF biomarkers and their structural imaging correlates in a large cohort of patients with different dementia and parkinsonian syndromes within the spectrum of frontotemporal lobar degeneration (FTLD). METHODS: We analyzed 3 CSF biomarkers (YKL-40, soluble β fragment of amyloid precursor protein [sAPPβ], neurofilament light [NfL]) and core Alzheimer disease (AD) biomarkers (β-amyloid1-42, total tau, phosphorylated tau) in patients with FTLD-related clinical syndromes (n = 159): behavioral variant of frontotemporal dementia (n = 68), nonfluent (n = 23) and semantic (n = 19) variants of primary progressive aphasia, progressive supranuclear palsy (n = 28), and corticobasal syndrome (n = 21). We also included patients with AD (n = 72) and cognitively normal controls (CN; n = 76). We compared cross-sectional biomarker levels between groups, studied their correlation with cortical thickness, and evaluated their potential diagnostic utility. RESULTS: Patients with FTLD-related syndromes had lower levels of sAPPβ than CN and patients with AD. The levels of sAPPβ showed a strong correlation with cortical structural changes in frontal and cingulate areas. NfL and YKL-40 levels were high in both the FTLD and AD groups compared to controls. In the receiver operating characteristic analysis, the sAPPβ/YKL-40 and NfL/sAPPβ ratios had areas under the curve of 0.91 and 0.96, respectively, distinguishing patients with FTLD from CN, and of 0.84 and 0.85, distinguishing patients with FTLD from patients with AD. CONCLUSIONS: The combination of sAPPβ with YKL-40 and with NfL in CSF could be useful to increase the certainty of the diagnosis of FTLD-related syndromes in clinical practice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CSF levels of sAPPβ, YKL-40, and NfL are useful to identify patients with FTLD-related syndromes.
OBJECTIVE: To analyze the clinical utility of 3 CSF biomarkers and their structural imaging correlates in a large cohort of patients with different dementia and parkinsonian syndromes within the spectrum of frontotemporal lobar degeneration (FTLD). METHODS: We analyzed 3 CSF biomarkers (YKL-40, soluble β fragment of amyloid precursor protein [sAPPβ], neurofilament light [NfL]) and core Alzheimer disease (AD) biomarkers (β-amyloid1-42, total tau, phosphorylated tau) in patients with FTLD-related clinical syndromes (n = 159): behavioral variant of frontotemporal dementia (n = 68), nonfluent (n = 23) and semantic (n = 19) variants of primary progressive aphasia, progressive supranuclear palsy (n = 28), and corticobasal syndrome (n = 21). We also included patients with AD (n = 72) and cognitively normal controls (CN; n = 76). We compared cross-sectional biomarker levels between groups, studied their correlation with cortical thickness, and evaluated their potential diagnostic utility. RESULTS:Patients with FTLD-related syndromes had lower levels of sAPPβ than CN and patients with AD. The levels of sAPPβ showed a strong correlation with cortical structural changes in frontal and cingulate areas. NfL and YKL-40 levels were high in both the FTLD and AD groups compared to controls. In the receiver operating characteristic analysis, the sAPPβ/YKL-40 and NfL/sAPPβ ratios had areas under the curve of 0.91 and 0.96, respectively, distinguishing patients with FTLD from CN, and of 0.84 and 0.85, distinguishing patients with FTLD from patients with AD. CONCLUSIONS: The combination of sAPPβ with YKL-40 and with NfL in CSF could be useful to increase the certainty of the diagnosis of FTLD-related syndromes in clinical practice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CSF levels of sAPPβ, YKL-40, and NfL are useful to identify patients with FTLD-related syndromes.
Authors: Ione O C Woollacott; Jennifer M Nicholas; Carolin Heller; Martha S Foiani; Katrina M Moore; Lucy L Russell; Ross W Paterson; Ashvini Keshavan; Jonathan M Schott; Jason D Warren; Amanda Heslegrave; Henrik Zetterberg; Jonathan D Rohrer Journal: Dement Geriatr Cogn Disord Date: 2020-04-28 Impact factor: 2.959
Authors: Ignacio Illán-Gala; Victor Montal; Sergi Borrego-Écija; Eduard Vilaplana; Jordi Pegueroles; Daniel Alcolea; Belén Sánchez-Saudinós; Jordi Clarimón; Janina Turón-Sans; Nuria Bargalló; Sofía González-Ortiz; Howard J Rosen; Maria Luisa Gorno-Tempini; Bruce L Miller; Albert Lladó; Ricard Rojas-García; Rafael Blesa; Raquel Sánchez-Valle; Alberto Lleó; Juan Fortea Journal: Brain Date: 2019-04-01 Impact factor: 13.501
Authors: Alberto Lleó; David J Irwin; Ignacio Illán-Gala; Corey T McMillan; David A Wolk; Edward B Lee; Vivianna M Van Deerlin; Leslie M Shaw; John Q Trojanowski; Murray Grossman Journal: JAMA Neurol Date: 2018-06-01 Impact factor: 18.302
Authors: Daniel Alcolea; David J Irwin; Ignacio Illán-Gala; Laia Muñoz; Jordi Clarimón; Corey T McMillan; Juan Fortea; Rafael Blesa; Edward B Lee; John Q Trojanowski; Murray Grossman; Alberto Lleó Journal: J Neurol Neurosurg Psychiatry Date: 2018-10-08 Impact factor: 10.154
Authors: Júlia Faura; Alejandro Bustamante; Anna Penalba; Dolors Giralt; Alba Simats; Elena Martínez-Sáez; Daniel Alcolea; Juan Fortea; Alberto Lleó; Charlotte E Teunissen; Wiesje M van der Flier; Laura Ibañez; Oscar Harari; Carlos Cruchaga; Mar Hernández-Guillamón; Pilar Delgado; Joan Montaner Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.472